Stirred Tank Bioreactor

ABSTRACT

The present invention is a disposable, presterilized bioreactor formed of molded plastic, having a top and body attached to each other. One or more ports are formed in the top, side and bottom of the housing. The one or more ports that are below the liquid/air interface level may be used as sampling ports, access ports for probes or drains or supply ports for liquids or gases. The bioreactor provides a direct retrofit for the existing glass or steel assembly that utilizes the existing support structures and controls. The molded design overcomes issues of discontinuity, dead spots and the like due to its fixed dimensions that are built in by the molding process. Reproducible probe and other equipment locations are guaranteed through the use of the molded port features.

CROSS-REFERENCED TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 12/387,688, filed May 6, 2009 which claims the benefit of U.S.Provisional Patent Application No. 61/131,640, filed on Jun. 11, 2008,the entire contents of which are incorporated by reference herein.

The present invention relates to a disposable stirred tank bioreactor.More particularly, it relates to a stirred tank reactor formed of amolded plastic having one or more ports molded therein.

BACKGROUND OF THE INVENTION

Many small scale bioreactors of the size from about 1 liter to about 200liters are formed of glass or steel, preferably stainless steel. Typicalvolumes for bench top versions are 2-10 liters. All have a solid bodyand a removable top sealed to the body by an o-ring. The top containsports for probes, sampling, air sparging, media exchange, and a stir rodfor circulation. They are typically used for culturing or fermentingvarious organisms such as plants, bacteria (e.g. E. coli), animal cells(e.g. Chinese Hamster Ovary (CHO) cells), yeast, mold, etc.

After each use (typically 3-15 days), the reactor and its componentsmust be disassembled, cleaned, reassembled, reconfigured and autoclavedbefore reuse. This is a time consuming, laborious process requiring thedisassembly and moving of many heavy and/or small and fragilecomponents. Additionally, one generally needs to validate the cleaningprocedure to ensure that it is done correctly time after time with thesame consistent results. At best after all the work has been completed,one has rendered the reactor and its components aseptically cleanmeaning that contamination can still occur by residual organisms oradvantageous ones that enter through the aseptic assembly.

Many designs have attempted to overcome these issues by using disposableliners in the glass or stainless tank.

U.S. Pat. No. 6,245,555 suggests using a plastic liner that is insertedwithin the existing tank to reduce the amount of cleaning and increasethe level of asepticness. However, it too has many limitations.

The liner must conform to the inner surface of the tank in order toprevent any discontinuity in the circulation within the device or toprevent the formation of dead spots or pockets in which material may gettrapped and fester or create uneven flow throughout the system. Howeverwrinkles in the liner still occur and create the above mentionedproblems. All ports are top mounted, limiting the available area for thedifferent components used in the bioreactor (feed lines, airlines,stirrer shafts, motors and journals, sampling ports, probe ports and thelike). Additionally, the top plate is releasably sealed to the linermaking only an aseptic connection. Often times the liner system islimited to an air sparging system for both gas transfer and circulation.The use of impeller shafts has been avoided due to the concern that theshaft or impellers may tear the liner during shipping, storage orassembly. Additionally, all probes and samplers enter through the lid ortop and have a tube that extends down into the liquid to the desiredlevel. This means that there is often a long dead leg of material thatneeds to be flushed or removed before and after sampling to ensure thatan accurate sample has been obtained. Lastly, lipids and cholesterolsare well-known to bind to many of the plastics used for such liners.

What is desired is a disposable tank liner that overcomes thedeficiencies with the current state of the art. The present inventionprovides such a device.

SUMMARY OF THE INVENTION

The present invention is a disposable bioreactor formed of moldedplastic so that it can be rigid or at least semi-rigid and can be heldin a stand or be self standing. The bioreactor is presterilized and hasa top and body sealed to each other. One or more ports are formed in thetop and side of the housing. Preferably at least one port is below theliquid/air level for the housing. The one or more ports that are belowthe liquid/air interface level may be used as sampling ports or accessports for probes. Using such a port allows one to take samples withoutthe need of the dip tube of the prior art eliminating the dead leg andrisk of an improper sample or contaminated sample. Additionally, theprobe does not need to be long in order to fit down to the desired levelin the container. It may simply extend sideways into the liquid at thedesired level. Ports below the liquid level are an ideal location forthe addition of disposable, optical sensors and provide a means forattaching sensing equipment.

The invention provides a direct retrofit for the existing glass or steelassembly that utilizes the existing support structures, probes formeasuring different parameters such as temperature and pH and controls.The molded design overcomes issues of discontinuity, dead spots and thelike due to its fixed dimensions that are built in by the moldingprocess. Reproducible probe and other equipment location is alsoguaranteed through the use of the molded port features. Moreover, therigid bowl is that it can accept the heating blanket that is used on theglass meaning that there is no need for an external support or heatingjacket. The molded plastic allows for greater flexibility in materialselection to reduce or eliminate lipid or cholesterol binding.Preferably the system allows for either an air sparging gas/circulationsystem and/or air sparging for gas transfer and a stirrer/impeller forcirculation with out fear of damage to the container. Molded containersare self supportive and do not require a support housing as does theflexible liner designs. Additionally with a molded plastic designheating or cooling blankets can be directly attached to the molded bodywhereas in a flexible bag the blanket must be installed either within oroutside of the support housing. Lastly by having one or more portsformed below the liquid/air level one can have a drain that allows forthe simple and near complete removal of all liquid when desired.

It is an object of the present invention to provide a bioreactor forculturing or processing a biomass formed of a presterilized, disposablehousing made of a plastic selected from the group consisting ofsemi-rigid and rigid plastic, said housing having a top and a bodyintegrally sealed to each other, the body having an interior space, oneor more ports formed in the top and the body respectively of the housingand in fluid communication with the interior of the housing, the one ormore ports having a cap to isolate the interior space of the body fromthe environment.

It is another object of the present invention to provide a bioreactorhaving two or more ports and at least one port is molded into the bodyat a level below a liquid/air interface of the housing.

It is a further object of the present invention to provide a bioreactorhaving the one or more ports are molded into the top and body.

It is an additional object of the present invention to provide abioreactor further comprising a stirrer shaft with one or more paddlesmounted within the body of the housing.

It is another object of the present invention to provide a bioreactor inwhich the body includes a port adjacent to a portion of the bodyfarthest from the top and the port farthest from the top includes an airdiffuser selectively retained to the interior of the body, the diffuserbeing formed of a frit selected from the group consisting plastic,ceramic and metal frits and the port being connected to a gas line onthe exterior portion of the body.

It is a further object of the present invention to provide a bioreactorhaving one or more ports wherein the one or more ports of the body areconnected to Luer fittings.

It is an object to provide a bioreactor having a stirrer shaft with oneor more paddles mounted within the body of the housing and a retainmenthub located at the bottom of the body of the bioreactor to retain andcenter the shaft.

These as well as other advantages which will become apparent form thedisclosure below.

In the Drawings

FIG. 1 shows a first embodiment of the present invention in perspectiveview.

FIG. 2 shows a first embodiment of the body of the present invention incross-sectional view.

FIG. 3 shows a first embodiment of the present invention incross-sectional view.

FIGS. 4A-4C show alternative stirring mechanisms of the presentinvention in cross-sectional view.

FIG. 5 shows an alternative embodiment of the body of the presentinvention in perspective view.

FIG. 6 shows one embodiment of the top according to the presentinvention in perspective view.

FIGS. 7A-7C show one type of fitting and its manner of attachment to onetype of port of the present invention in perspective view.

FIG. 8 shows an alternative embodiment of the present invention.

FIG. 9 shows one embodiment of the top according to the presentinvention in perspective view.

FIG. 10 shows one embodiment of the bottom of the bioreactor accordingto the present invention in perspective view.

FIG. 11 shows one embodiment of a different support that interfaces withthe bottom of the bioreactor shown in FIG. 10 according to the presentinvention in perspective view.

FIG. 12 shows the bioreactor of FIG. 10 connected to the base of FIG. 11in perspective view.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 shows an embodiment of the present invention. The bioreactor 2 isheld in a stand 4 which is comprised of several legs 6 (in thisembodiment 3 legs although one continuous leg or 2 large legs or morethan 3 legs can also be used) and a support rim 8. As shown the legs 6may have an optional support piece 10 at or near the bottom to keep thelegs 6 from spreading when the bioreactor 2 is filled and in the stand4.

Depending upon the type of circulation system used the stand 4 may alsosupport the drive mechanism 12 (as shown) for the circulation mechanism,which typically is a stirrer or paddle assembly 14 as will be describedin greater detail later. In this particular embodiment, the drivemechanism 12 is a motor and is mounted to the top of the centered abovethe top 16 of the bioreactor 2 by several arms 18 (although 3 are shownalternative numbers may be used). Other features such as mounting blocks(not shown) and the like may be formed on the top 16 or support rim 8 tosupport the drive mechanism 12. As shown the drive mechanism 12 has ashaft 20 that can be attached to the stirrer as explained later herein.Other stands can be used in lieu of the design described above and willwork equally well.

The bioreactor body 22 has an interior space into which the fluids,cells, probes and other devices of the bioreactor are at least partiallycontained. The body 22 is sealably attached to the top 16. This may beby a mechanical seal such as a rubber gasket and clips 24 (as shown) orby a clamp, such as a band clamp or Ladish or TriClover clamp, matedthreads on the top 16 and body 22 and the like. Alternatively, they maybe sealed by adhesives or heat sealing of the top 16 to the body 22 orformed together in one piece such as in a rotomolding apparatus.

The body 22 has one or more sidewalls 26 that extend downwardly from thetop 16 and terminate in a closed bottom 28, preferably having ahemispherical shape. As shown, there is one sidewall 26 of a circulardesign which is a retrofit for existing glass and metal bodies.Alternatively, there can be 3, 4, or more sidewalls if desired (notshown).

Preferably, the body is made of a single piece of molded plastic.Alternatively it may be made of two or more pieces of plastic that aresealed together such as by heat, glue, or gaskets (not shown).

In another alternative arrangement shown in FIG. 5, only the top 16 aand bottom 28 a are made of molded plastic and the one side wall 26 a inthis embodiment is formed of flexible plastic such as a plastic film.This still allows for the use of one or more ports in the device belowthe liquid/air level. Also notice that the port(s) such as 32 a mayterminate in a hose barb or other connective feature if desired.

Also formed in the bioreactor 2 of this embodiment are one or more ports30 (in this embodiment there are three types 30 a-c (for a total of 5ports) formed in the top 16 and one or more ports 32 in the body 22 (inthis embodiment there are at least two different types 32 a-b for atotal of seven ports overall in this embodiment). The top 16 and body 22may have multiple ports of similar and/or of different styles to provideone with the number of ports, of the desired type, in the desiredlocations throughout the bioreactor 2. These ports 30, 32 or at least aportion of them are formed as part of the top 16 and/or body 22. Theymay be formed with threads that mate to sealable covers such as closedcaps, gasketed caps with a throughbore within the gasket, or variousLuer fittings. Alternatively, one or more of the ports can be made inthe plastic top 16 and/or body 22 by drilling or burning a hole and thenmounting (such as by heat bonding or adhesives) a port in place throughor around the hole. Many different port styles and sizes can beaccommodated in this invention.

Ports 30 a may be used for liquid or gas entrance or exit or for probessuch as pH probes, thermometers or thermocouples or the like. Ports 30 bmay be used for similar purposes. Port 30 c is for the stirrer shaftdescribed in further detail herein. Alternatively, if the bioreactor isan airlift design and doesn't use a stirrer rod, the port 30 c may beused to house the airline to the sparger at or near the bottom of thebody or for any other desired purpose. Ports 32 a may be used forsampling of the liquid or for probes such as pH, temperature, dissolvedoxygen, lactose level, etc as are common on such bioreactors. Ports 32 awhile shown as being formed on the sidewall 26 may also be formed in thebottom if desired as shown in FIG. 2. Port 32 b is valved port which canbe used to supply gas to the body 22 and/or as a drain or outlet fromthe body. It may serve both functions by attaching a 3 position valve orY-shaped tube with valves such as pinch valves on each arm of the Y tocontrol flow (not shown). One suitable system for the valve of port 32 bis a LYNX® connector available from Millipore Corporation of Billerica,Mass. and as shown in US2005/0016620.

Preferably, one or more ports 32 of the body are formed in a locationthat is below the normal liquid/gas interface level of the bioreactor.

If desired, one or more of the ports 32 a or b in FIGS. 1 and/or 2 maybe used to provide gases to the body's interior. A plastic frit such asa POREX® microporous membrane or ceramic stone or sintered metal filtermay be attached to the inside of the port within the body to provide thesized gas bubbles desired. Alternatively, a port 30 a in the top 16 maybe used to hold a tube that extends down into the body to provide thegas supply. Again it may use a frit or ceramic stone or sintered metalfilter to provide the desired bubble size.

FIG. 3 shows a bioreactor 2 with top 16 and body 22 sealed to each otherand the stirring mechanism 14 in place. The stirring mechanism is formedof a shaft 40 and one or more paddles 42. The shaft 40 extends throughport 30 c and is connected to the shaft 20 of the drive mechanism 12(not shown). Preferably one or more o-rings in the port 30 c allow formovement of the shaft 40 without compromising the integrity of the sealwithin the body 22.

FIG. 4A shows a stirrer 14 and a retainment hub 50 formed in the bottomof the body 22. The retainment hub 50 locates and holds a portion of theshaft so that the shaft does not become dislodged during shipping,storage or use. Also an optional element, vanes 43 is shown in FIG. 4A.These vanes can be molded into the inner surface of the body 22 andextend outward into the interior or they may be separately added aftermolding. The vanes 43 help to direct flow and ensure that adequatemixing occurs within the bioreactor 2.

FIGS. 4B and C show an alternative design to the stirrer 14. In thisembodiment, the gas supply line is built into the stirrer shaft 40. Theshaft 40 has a hollow central bore 44 running through at least a portionof the shaft. At or near the bottom of the shaft 40 is a gas outlet 46which may contain a frit, ceramic stone or sintered metal filter 52 tocreate the desired bubble size. Gas enters the bore 44 through gas port48 in port 30 a. One or more gas conduits 54 connect the inner portionof the port 30 a with the bore 44. One or more, in this instance 2gaskets 56 such as o-rings are mounted above and/or below the gas port48 to ensure the gas flows through the port 48 and into the bore 44through conduit(s) 54 and does not escape to the atmosphere orcompromise the integrity of the body. In use the gas flows from a supplyinto port 48 then into conduit(s) 54 and down the central bore 44 to thegas outlet 46 in the shaft and then into the inner volume of the body22.

FIG. 6 show one embodiment of the top 16 with some of the various portconfigurations and styles that are possible with the present invention.For example port 30 a may be a screw thread style of port into which agas or liquid line or probe with matching mating threads is threaded tocreate a liquid tight seal.

FIGS. 7A-C show another port/fitting style. The fitting 31 as shown inFIG. 7C has cam lock 33. This cam lock mates with a mating cam lockholder 35 in the port 30 (FIG. 7B). The fitting 31 is inserted into port30 by first aligning the cam locks 33 of the fitting 31 with the camopening 35 of the port 30. It is then pushed downward and rotated toride over the cam ramp 37 and terminate and seat itself in the cam lockretainer 39 of the port 30.

FIG. 8 shows an alternative embodiment of the present inventionincorporating a magnetic mixer 101 within the body 14 driven remotelyfrom a magnetic drive 100 located on the outer surface of the body 14.

FIG. 9 shows an alternative top 16 of the invention to that shown inFIG. 6 in that at least one or more portions of the top 16 incorporatestube clips 202 which can hold the various tubes of the system in anorganized and orderly arrangement. Preferably, the tube clips 202 areformed on an outer edge 200 of the top 16 although if desired some orall of them may also be attached to the upper surface of the top (notshown). In this illustrated embodiment, four clips 202 are shownalthough more or less may be used if desired. Preferably they are moldedas part of the top 16. Alternatively, they may be separately attached bymelt bonding, solvent bonding or glues, if desired. Likewise, some orall of the ports, 30 b′ and 30 b″, can be in the form of hose barbs asshown rather than screw ports 30 or Luer type fittings as shown in FIG.6, cam locks of FIG. 7 or other types of fittings discussed below andcommonly used by one of ordinary skill in the art. Tubes attached to ahose barb fitting such as 30 b′ can have tie wraps, connectors such asthose taught by US2008/0284163A1 or other devices or can be adhered tothe hose barb to keep the tubes in place even when under any pressurethat may occur in the system.

FIG. 10 shows an alternative bottom portion 28 of the bioreactor 2 tothat shown in FIGS. 1-3. In this embodiment, instead of using the stand6, the bottom outer wall 204 has two or more, preferably three or four,locking tabs 206 either molded as a feature of the bottom outer wall 204or separately formed and attached to the bottom outer wall 204 such asby heat bonding, solvent bonding or glue.

The locking tabs 206 of the bottom outer wall 204 mate to correspondinglocking features 208 of a bottom support 210 shown in FIG. 11. Thebioreactor is placed into the support 210 and the locking tabs 206 ofthe bottom outer wall 204 engage with the locking features 208 of thesupport 210. This secures the bioreactor 2 to the support 210 so thatthe bioreactor 2 is held upright in a secure manner as shown in FIG. 12.Additionally, if desired, one or more open slots 212 can be formed inthe support 210 so that any tubing or other features that extend outfrom the bioreactor 2 when the bioreactor and support are mated can beaccommodated without removal or pinching. As shown the tabs and features206,208 are threaded style devices. However they can be other forms suchas cam locks and cam lock holders as used in some of the portembodiments discussed above. The locking feature allows the end user toremove the base from bowl and recycle easily since the base is not incontact with the culture medium and thus does not need to be sterilized.

Fittings such as compression fittings and tube weld, hose barb and pipethreads, when molded directly into the body, reduce holdup volume andsimplify the system. Such components are well known and the covers,connectors, septums for sampling (also called piercable needle ports),check or other valves and the like, whether Luer type or not; Luer Lok®fittings; and the like are readily available for mating with these portsfrom a variety of companies such as Value Plastics, Inc of Fort Collins,Colo.

Suitable polymers which can be used to form the top and body include butare not limited to polycarbonates, polyesters, nylons. PTFE resins andother fluoropolymers, acrylic and methacrylic resins and copolymers,polysulphones, polyethersulphones, polyarylsulphones, polystyrenes,polyetherimides, nylons, polyesters, polyethylene terephthalates (PET),polyvinyl chlorides, chlorinated polyvinyl chlorides, ABS and its alloysand blends, polyolefins, preferably polyethylenes such as linear lowdensity polyethylene, low density polyethylene, high densitypolyethylene, and ultrahigh molecular weight polyethylene and copolymersthereof, polypropylene and copolymers thereof and metallocene generatedpolyolefins.

Preferred polymers are polyolefins, in particular polyethylenes andtheir copolymers; polystyrenes; and polycarbonates.

The top and body may be made of the same polymer or different polymersas desired.

Likewise, the polymers may be clear or rendered optically opaque orlight impermeable. When using opaque or light impermeable polymers, itis preferred that their use be limited to the side walls so that one mayuse optical scanners or readers on the bottom portion to detect thevarious parameters of the liquid within the bioreactor.

Most of the bioreactors of the present invention are injection molded,but they can be rotoformed in the case that a jacketed body is requiredor unique featured are added which are best accomplished via rotomoldingtechniques.

An additional advantage to a molded or rigid formed plastic body is thatheating or cooling blankets can be easily attached to them.

In practice, the body is designed as desired, preferably with asubstantially flat open rim one circular sidewall extending downwardlyfrom the rim and terminating in a rounded bottom as shown in FIG. 1. Thebody is preferably made of molded plastic such as polystyrene,preferably with some or all of the desired ports, including one or moreports formed in the sidewall and more preferably with one or more portsformed in the sidewall at a level below the anticipated liquid/airlevel. The top is separately molded with some or all of its desiredports being molded in place. In many molding applications the ports willactually contain flash or be closed off by a thin plastic layer thatneeds to be removed in order to open up the ports. Alternatively, asdiscussed above, the ports may be formed after molding by drilling holesat the appropriate places and adding port fittings in place in a liquidtight manner.

Caps such as various Luer fittings including threaded caps, Luer basedseptum covers, Luer Lok caps, closed Luer or other threaded caps, plugs,tubes attached to the ports formed with hose barb fittings and the likeare attached to the one or more ports.

If used, the stirrer shaft 40 with impeller(s) 42 is inserted into theport 30 in the top 16 and the bottom of the shaft 40 is centered andretained within hub 50. The top 16 is then sealed to the body 22 such asby the clips 24 or by heat sealing or adhesive.

Depending upon the type of probe and the sterilization technique chosen,one or more of the probes may be added and sealed in place at this time.

The closed bioreactor is then sterilized, packaged and sent to the user.

The bioreactor may be sterilized by many different techniques. The mostcommon would be by radiation especially gamma and to a lesser extent,beta radiation. In this embodiment, many probes are not gamma stable andwould need to be aseptically assembled into the bioreactor at the user'sfacility.

Another method is to use gases such as ethylene oxide. In this type ofsterilization, one could use the various ports to supply y the gas andthen remove it from the interior of the bioreactor. This may be adedicated port(s) or it may then be used for another purpose such as adrain or liquid/air movement.

Alternatively, the device may be sterilized by autoclaving with steamand preferably super heated steam and pressure. In this embodiment, avent (not shown) to remove the steam would be a useful addition to oneof the ports (30 or 32).

The sterile device is placed within the stand and the variousconnections for air, liquid, probes, sampling, etc are attached to thedevice at the appropriate ports. The device is filled with media to adesired level forming a liquid/air interface somewhere below where thetop 16 is attached to the body 22 to leave a head space of gas as iscommon in such devices. At least one port 32 is below the level of theinterface.

The media is then seeded with the organism to be grown, be it plant,animal cell (CHO or NSO cells for instance) virus, yeast, mold orbacteria (such as E. coli) and the liquid is circulated and air/gasesand liquids moved into or out of the device in a manner to effectivelygrow the culture inside.

After a suitable time, the cells may be harvested either by drawing offthe liquid, leaving the cells behind, or in the instance where the cellsneed to be ruptured to recover the desired product by either removingthe cells and then rupturing them or rupturing them in the device andthen removing the ruptured mass for further processing. Additionally,with the vast number of available ports one could use the device to runa perfusion reactor in which small amounts of cells or expressed productis removed on a continual basis for further processing while the cellswithin the device continue to grow and make the desired product.

Once the process is completed the device is drained and all connectionsremoved and the device ports are sealed. It is then disposed of properlysuch as by incineration.

What is claimed: 1) A bioreactor for culturing, fermenting or processing a biomass comprising: a presterilized, disposable housing made of a rigid plastic, said housing having a top and a body releasably sealed to each other, wherein the top and body are sealed to each other by a gasket interposed between the top and body and a mechanical means for releasably holding the top and body together, the body having an interior space, a first set of one or more access ports formed in the top of the housing and in fluid communication with the interior of the housing, a second set of one or more access ports formed in the body and bottom of the housing and in fluid communication with the interior of the housing wherein at least one access port of the second set being a valved port in the bottom of the housing forming an outlet for liquid in the housing, wherein the valved port further allows for the entrance of gases into the housing through the port by the valve having a first position to allow liquid flow, a second position to allow gas flow and a third position to allow neither liquid nor gas to flow through the valve and at least one access port of the second set being formed in the body of the housing so as to allow for the introduction of liquid, probes or samplers into the interior of the body, the one or more access ports having a cap to isolate the interior space of the body from the environment. 2) A bioreactor for culturing, fermenting or processing a biomass comprising: a presterilized, disposable housing made of a rigid plastic, said housing having a top and a body releasably sealed to each other, the body having an interior space, a first set of one or more access ports formed in the top of the housing, a second set of one or more access ports formed in the body and bottom of the housing and in fluid communication with the interior of the housing wherein at least one access port of the second set being a valved port in the bottom of the housing forming an outlet for liquid in the housing, wherein the valved port further allows for the entrance of gases into the housing by a valve selected to control flow between gas and liquid through the port, and at least one access port of the second set being formed in the body of the housing and in fluid communication with the interior of the housing so as to allow for the introduction of liquid, probes or samplers into the interior of the body, the one or more access ports of the first and second set having a cap to isolate the interior space of the body from the environment, the top and body are releasably sealed to each other by a gasket interposed between the top and body and a mechanical means for holding the top and body together and wherein the mechanical means is selected from the group consisting of clips and clamps. 3) A bioreactor for culturing, fermenting or processing a biomass comprising: a presterilized, disposable housing made of a rigid plastic, said housing having a top and a body releasably sealed to each other, the body having an interior space, a first set of one or more access ports formed in the top of the housing, a second set of one or more access ports formed in the body and bottom of the housing and in fluid communication with the interior of the housing wherein at least one access port of the second set being a valved port in the bottom of the housing forming an outlet for liquid in the housing, and wherein the valved port further allows for the entrance of gases into the housing by a valve selected from the group consisting of a 3 position valve and Y-shaped tube with valves on each arm of the Y to control flow between gas and liquid through the port and at least one access port of the second set being formed in the body of the housing and in fluid communication with the interior of the housing so as to allow for the introduction of liquid, probes or samplers into the interior of the body, the one or more access ports of the first and second set having a cap to isolate the interior space of the body from the environment, the top and body are releasably sealed to each other by a gasket interposed between the top and body and a mechanical means for holding the top and body together and wherein the mechanical means is selected from the group consisting of clips and clamps and wherein an outer wall of the bottom portion of the housing has two or more locking tabs and further comprising a stand having two or more locking features that interact with the locking tabs of the housing when the housing is inserted into the stand to hold the housing in the stand in an upright and secure manner. 4) The bioreactor of claim 1 wherein the valve of the valved port is formed of a 3 position valve and Y-shaped tube with valves on each arm of the Y to control flow between gas and liquid through the port. 5) The bioreactor of claim 2 wherein the valved port further allows for the entrance of gases into the housing by a valve selected from the group consisting of a 3 position valve and Y-shaped tube with valves on each arm of the Y to control flow between gas and liquid through the port. 6) The bioreactor of claim 1 wherein an outer wall of the bottom portion of the housing has two or more locking tabs and further comprising a stand having two or more locking features that interact with the locking tabs of the housing to hold the housing in the stand in an upright and secure manner. 7) The bioreactor of claim 2 wherein an outer wall of the bottom portion of the housing has two or more locking tabs and further comprising a stand having two or more locking features that interact with the locking tabs of the housing when the housing is inserted into the stand to hold the housing in the stand in an upright and secure manner. 